哮喘患者白三烯代谢与孟鲁司特疗效的研究

目的:探讨支气管哮喘白三烯代谢与孟鲁司特抗白三烯治疗临床疗效的相关性,评估影响疗效的因素,为选择用药提供指导。方法:对48例轻-中度稳定期哮喘患者进行4周孟鲁司特治疗试验。观察症状积分、β2R激动剂用量、血Eos%、血清总IgE、肺功能、尿白三烯E4(uLTE4)的变化。最终疗效评判标准,符合下列三者为有效:症状积分下降值>20%,β2R激动剂用量下降值>20%,及1秒量(FEV1)提高值>10%;其它均为无效。二分类Logistic回归分析观察指标与疗效的相关性。结果:25例有明显临床改善;23例无明显改善。有效组患者uLTE4明显高于无效组(224.5±34.4vs175.3±37.1 ng/g creatinine,P<0.05);而Eos%、血清IgE、肺功能均无统计学差异(P>0.05)。Spearman回归分析提示,有效组治疗前一秒量占预计值的百分比(FEV1/预计值%)与uLTE4存在负相关性(r=-0.352,P<0.05)。Logistic回归分析示孟鲁司特疗效与uLTE4有相关性。当uLTE4≥200 ng/g creatinine时,其OR=3.5,95%CI为(1.7,15.8);其它指标则无相关性。结论:uLTE4水平与孟鲁司特治疗临床疗效密切相关,可作为选择此类药物的参考标志物。

Study on Relationship Between Urinary Levels of Cysteinyl Leukotriene E4 Measurement Metabolism Level and Clinical Response to Antileukotriene Montelukast Treatment in Patients with Asthma

Objective: To investigate the relationship between urinary cysteinyl leukotrienes and clinical response to montelukast treatment in asthma,for the further decision of pharmacologic scheme.Methods: Forty-eight patients with stable mild-moderate asthma were treated with montelukast for four weeks.Asthmatic symptom scores,β_2-agonist dosage,percentage of eosinophil,total serum IgE,forced expiratory volume in the first second(FEV_1),peak expiratory flow rate(PEFR) and urinary leukotriene E_4(uLTE_4) were recorded for the clinical response analysis.Therapy responders were the patients with a reduction of >20% in mean symptom scores,a reduction of>20% in β_2-agonist usage and a mean improvement of FEV_1>10% from baseline value.Binary logistic regression was used to access the various clinical factors correlated with clinical responses.Results: There were 25 responders and 23 non-responders.The mean uLTE_4 level from the responders was higher than that from the non-responders(224.5±34.4 vs 175.3±37.1 ng/g creatinine,P<0.05).Spearman regression analysis showed there was negative correlation between uLTE_4 and percentage predicted FEV_1 at baseline in the responders(r=-0.352;P<(0.05).) Logistic analysis showed that there was a significant correlation between the clinical response and uLTE_4,but no relation was found between clinical response with other indices(P>(0.05).) Subjects with uLTE_4 level ≥200 ng/g creatinine were 3.5 times more likely to respond to it than those with <200 ng/g creatinine(95%CI: 1.7-15.8).Conclusion: The uLTE_4 level is closely correlated with montelukast antileukotriene treatment.And uLTE_4 is a good biomarker for selecting this drug in asthma patients.